This is an application for a K23 award for Dr. Andy Choi, an instructor in nephrology at the University of California San Francisco and a young patient-oriented researcher in the area of HIV-related kidney disease. This K23 award will provide Dr. Choi with training and mentored research experience in the following areas: (1) recruiting and maintaining a patient cohort;(2) performing physiologic measurements in patients, (3) expertise in GFR measurement, (4) training in translational HIV medicine, (5) statistical methods for comparing measurement techniques and diagnostic tests, and (6) designing and implementing pilot intervention studies. To achieve these training goals, Dr. Choi has assembled a mentoring team comprised of a primary mentor, Dr. Michael Shlipak, Chief of General Internal Medicine at the San Francisco VA Medical Center, who is an epidemiologist in kidney disease and a national expert in the use of cystatin C, and 3 co-mentors: Dr. Carl Grunfeld, an expert in the metabolic complications of HIV-infection and in performing physiologic measurements in human subjects;Dr. Jeffrey Martin, an epidemiologist and codirector of the Study of the Consequences of the Protease Inhibitor Era (SCOPE);and Dr. Peter Bacchetti, an expert in the biostatistical methods for studying longitudinal outcomes among HIV-infected patients. Cystatin C is a novel measure of kidney function that has been found to be a more sensitive test than creatinine for the diagnosis of kidney disease in several populations. In order to establish which marker of kidney disease is most accurate in the HIV-infected population, we will measure cystatin C, serum creatinine, body composition, and the gold standard of directly measured GFR in a subset of patients enrolled in the SCOPE cohort. The specific aims of this K23 grant are to compare the performance of creatinine-based estimates of kidney function and cystatin C with directly measured GFR using iothalamate clearance;to reassess previously recognized risk factors of kidney dysfunction using gold standard GFR;and to describe novel risk factors associated with kidney function decline in HIV-infected persons. PUBLIC HEALTH RELEVANCE: Better methods for detecting renal dysfunction will improve our ability to accurately diagnosis and stage kidney disease, to make adjustments to dosing of HAART medications and to monitor for renal toxicity, and to assess promising interventions to detect and treat early stages of kidney disease.